230

Exp Physiol 100.3 (2015) p 230

Viewpoint Viewpoint

The many facets of electrical stimulation of vagus nerves Benjamin J. Scherlag

ExperimentalPhysiology

Email: [email protected]

Vagus nerve stimulation (VNS) has been used for treating patients with epilepsy refractory to drug therapy and, more recently, for amelioration of clinical heart failure. In this issue of Experimental Physiology, Huang et al. (2015) applied VNS, which slowed the heart rate by 10% and reversed the deleterious electrophysiological effects induced by 4 hours of left stellate ganglion stimulation. Importantly, VNS was effective in significantly increasing the ventricular fibrillation threshold when applied during the last 2 h of left stellate ganglion stimulation, i.e. in the context of a hyperactive sympathetic state. The authors cite experimental studies in which different forms of induced sympathetic hyperactivity increase the slope of the ventricular restitution curve and decrease the ventricular fibrillation threshold, thereby promoting ventricular tachyarrhythmias. Recent literature has brought VNS to the forefront as an antiarrhythmic agency, but the mechanisms underlying these actions have not been fully elucidated. Huang et al. (2015) have focused primarily on the ventricular properties that were modified as a result of the induced hypersympathetic state and the reversal of these effects by VNS. An emerging aspect of VNS at relatively low levels has been the modulation of autonomic effects on various organ systems. With regard to the heart, VNS, which slowed the heart rate, abruptly eliminated neural firing recorded from the anterior right ganglionated plexi (ARGP) on the atrium (Zhang et al. 2009). In another experimental study, Scherlag et al. (2005) induced sinus tachycardia by injection of a sympathomimetic into the ARGP, inducing a hyperactive sympathetic state. In 40% of these instances, in the dog heart, there was a concomitant increase in systolic blood pressure and ventricular arrhythmias along with sinus tachycardia, suggesting

DOI: 10.1113/expphysiol.2014.083956

neural connections between the ARGP and neural elements on the ventricles inducing sympathetic actions. Directly related to these findings is a study showing that ablation of the ganglionated plexi increases the risk of ventricular arrhythmias in an experimental preparation with acute myocardial ischaemia, another example of a hyperactive sympathetic state (He et al. 2013a). Another facet of the autonomic modulating action of VNS has recently been demonstrated repeatedly, in that low-level VNS, well below the intensity that slows the heart rate or affects AV conduction, can also inhibit ARGP firing and have a significant antiarrhythmic action in the atrium by suppressing induced atrial fibrillation (Yu et al. 2011). Associated with this action is the release of a neurotransmitter/neuromodulator, vasostatin-1. This 76-amino-acid peptide acts via nitric oxide to provide a strong antiadrenergic action. These findings of the effects of low-level VNS have recently been extended to ventricular function and electrophysiology in the normal heart and after the induction of myocardial ischaemia/infarction (He et al. 2013b). A common denominator mechanism whereby VNS acts as an antifibrillatory agent in the atria and ventricles may be due, in part, to the antiadrenergic effect of VNS by suppressing sympathetic hyperactivity at the level of the intrathoracic (stellate) ganglia or the intrinsic cardiac ganglionated plexi. The study by Huang et al. (2015) extends the ameliorative actions of VNS on several electrophysiological properties of the ventricles in hyperactive sympathetic conditions. As the authors state, ‘ . . . increased sympathetic tone and reduced vagal tone are associated with increased risk of life-threatening ventricular arrhythmias both in myocardial infarction patients and heart failure patients . . . Future clinical studies are warranted to assess the safety and effectiveness of VNS for the management of ventricular arrhythmias . . . ’ in these patients. The implication of these studies and others recently published add to the emerging evidence of the role of neural/neurohumoral modulation that

is operative at different levels and different types of VNS to prevent and/or treat ventricular functional pathologies as well as life-threatening cardiac arrhythmias. It should be noted that numerous neurotransmitters and neuromodulators, such as angiotensin II, bradykinin, substance P, vasointestinal peptide and adenosine, have been associated with the many facets of VNS at the intrinsic ganglia on the heart and at other effector organ sites innervated by the vagus nerves. What role each of these agents released as a result of VNS might play in affecting cardiac electrophysiological properties in the normal and hyperactive physiological state remains to be determined in further investigations. References He B, Lu Z, He W, Wu L, Cui B, Hu X, Yu L, Huang C & Jiang H (2013a). Effects of ganglionated plexi ablation on ventricular electrophysiological properties in normal hearts and after acute myocardial ischemia. Int J Cardiol 168, 86–93. He B, Lu Z, He W, Wu L, Huang B, Yu L, Cui B, Hu X & Jiang H (2013b). Effects of lowintensity atrial ganglionated plexi stimulation on ventricular electrophysiology and arrhythmogenesis. Auton Neurosci 174, 54–60. Huang J, Qian J, Yao W, Wang N, Zhang Z, Cao C, Song B & Zhang Z (2015). Vagus nerve stimulation reverses ventricular electrophysiological changes induced by hypersympathetic nerve activity. Exp Physiol 100, 239–248. Scherlag BJ, Yamanashi WS, Amin R, Lazzara R & Jackman WM (2005). Experimental model of inappropriate sinus tachycardia: initiation and ablation. J Interv Card Electrophysiol 13, 21–29. Yu L, Scherlag BJ, Li S, Sheng X, Lu Z, Nakagawa H, Zhang Y, Jackman WM, Lazzara R, Jiang H & Po SS (2011). Low-level vagosympathetic nerve stimulation inhibits atrial fibrillation inducibility: direct evidence by neural recordings from intrinsic cardiac ganglia. J Cardiovasc Electrophysiol 22, 455–463. Zhang Y, Scherlag BJ, Lu Z, Niu GD, Yamanashi WS, Hogan C, Fields J, Ghias M, Lazzara R, Jackman WM & Po SS (2009). Comparison of atrial fibrillation inducibility by electrical stimulation of either the extrinsic or the intrinsic autonomic nervous systems. J Interv Card Electrophysiol 24, 5–10.

 C 2015 The Authors. Experimental Physiology  C 2015 The Physiological Society

Copyright of Experimental Physiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.

The many facets of electrical stimulation of vagus nerves.

The many facets of electrical stimulation of vagus nerves. - PDF Download Free
51KB Sizes 0 Downloads 7 Views